Apparatus and Methods for Determining Damaged Tissue Using Sub-Epidermal Moisture Measurements

ABSTRACT

The present disclosure provides apparatuses and computer readable media for measuring sub-epidermal moisture in patients to determine damaged tissue for clinical intervention. The present disclosure also provides methods for determining damaged tissue.

RELATED CASES

This application is a continuation of U.S. application Ser. No.15/280,487, filed Sep. 29, 2016, and U.S. application Ser. No.15/280,528, filed Sep. 29, 2016, now U.S. Pat. No. 9,763,596, issuedJan. 19, 2017, which are continuations of U.S. application Ser. No.15/273,202, filed Sep. 22, 2016, now U.S. Pat. No. 10,178,961, issuedJan. 15, 2019, which is a continuation of U.S. application Ser. No.15/134,110, filed Apr. 20, 2016, now U.S. Pat. No. 10,192,740, issuedJan. 22, 2019, which claims priority to U.S. Provisional ApplicationSer. No. 62/152,549, filed Apr. 24, 2015, the entirety of each of whichis incorporated by reference herein. All references referred to hereinare herein incorporated by reference in their entireties.

FIELD OF INVENTION

The present disclosure provides apparatuses and computer readable mediafor measuring sub-epidermal moisture in patients to determine damagedtissue for clinical intervention. The present disclosure also providesmethods for determining damaged tissue.

BACKGROUND

The skin is the largest organ in the human body. It is readily exposedto different kinds of damages and injuries. When the skin and itssurrounding tissues are unable to redistribute external pressure andmechanical forces, pressure ulcers may be formed. Pressure ulcers pose asignificant health and economic concern internationally, across bothacute and long-term care settings. Pressure ulcers impact approximately2.5 million people a year in the United States and an equivalent numberin the European Union. In long-term and critical care settings, up to25% of elderly and immobile patients develop pressure ulcers.Approximately 60,000 U.S. patients die per year due to infection andother complications from pressure ulcers.

Most pressure ulcers occur over bony prominences, where there is lesstissue for compression and the pressure gradient within the vascularnetwork is altered. Pressure ulcers are categorized in one of fourstages, ranging from the earliest stage currently recognized, in whichthe skin remains intact but may appear red over a bony prominence (Stage1), to the last stage, in which tissue is broken and bone, tendon ormuscle is exposed (Stage 4). Detecting pressure ulcers before the skinbreaks and treating them to avoid progression to later stages is a goalof policy makers and care providers in major economies. Most pressureulcers are preventable, and if identified before the first stage ofulceration, deterioration of the underlying tissue can be halted.

Of the four main stages of pressure ulcers, the earliest stage currentlyrecognized (Stage 1) is the least expensive to treat at an average of$2,000 per ulcer, but is also the hardest to detect. In many cases,injuries on the epidermis layer are not present or apparent when theunderlying subcutaneous tissue has become necrotic. As a result, it iscommon that a clinician's first diagnosis of a pressure ulcer in apatient occurs at late stages of the ulcer development—at which time theaverage cost of treatment is $43,000 per Stage 3 ulcer, or $129,000 perStage 4 ulcer. If clinicians could identify and diagnose pressure ulcersat earlier stages of ulcer development, the healing process would beconsiderably shortened and the treatment costs would be significantlylower.

To treat pressure ulcers in a timely and effective manner, cliniciansneed to be able to identify, with precision, the ulceration area.However, the current standard to detect pressure ulcers is by visualinspection, which is subjective, unreliable, untimely, and lacksspecificity.

SUMMARY OF THE INVENTION

In an aspect, the present disclosure provides for, and includes, anapparatus for identifying damaged tissue. The apparatus may comprise oneor more electrodes capable of interrogating tissue at and around ananatomical site, where each of the one or more electrodes may beconfigured to emit and receive a radiofrequency signal to generate abioimpedance signal; a circuit that may be electronically coupled to theone or more electrodes and may be configured to convert the bioimpedancesignal into a sub-epidermal moisture (“SEM”) value; a processor that maybe electronically coupled to the circuit and may be configured toreceive the SEM value; and a non-transitory computer readable mediumthat may be electronically coupled to the processor and may compriseinstructions stored thereon that, when executed on the processor, mayperform the steps of receiving from the processor a SEM value measuredat the anatomical site and at least two SEM values measured around theanatomical site and their relative measurement locations; determining amaximum SEM value from the measurements around the anatomical site;determining a difference between the maximum SEM value and each of theat least two SEM values measured around the anatomical site; andflagging the relative measurement locations associated with a differencegreater than a predetermined value as damaged tissue. In another aspect,a difference is determined between the maximum SEM value and a minimumSEM value measured around the anatomical site.

In yet another aspect, the apparatus may comprise one or more electrodescapable of interrogating tissue at and around an anatomical site, whereeach of the one or more electrodes may be configured to emit and receivea radiofrequency signal to generate a bioimpedance signal; a circuitthat may be electronically coupled to the one or more electrodes and maybe configured to convert the bioimpedance signal into a SEM value; aprocessor that may be electronically coupled to the circuit and may beconfigured to receive the SEM value; and a non-transitory computerreadable medium that may be electronically coupled to the processor andmay comprise instructions stored thereon that, when executed on theprocessor, may perform the steps of receiving from the processor a SEMvalue measured at the anatomical site and at least two SEM valuesmeasured around the anatomical site and their relative measurementlocations; determining an average SEM value for each group of SEM valuesmeasured at approximately equidistance from the anatomical site;determining a maximum SEM value from the average SEM values; determininga difference between the maximum average SEM value and each of theaverage SEM values measured around the anatomical site; and flagging therelative measurement locations associated with a difference greater thana predetermined value as damaged tissue.

In yet another aspect, the present disclosure provides for, andincludes, a non-transitory computer readable medium for identifyingdamaged tissue. The non-transitory computer readable medium may compriseinstructions stored thereon, that when executed on a processor, mayperform the steps of receiving a SEM value at an anatomical site and atleast two SEM values measured around the anatomical site and theirrelative measurement locations; determining a maximum SEM value from themeasurements around the anatomical site, determining a differencebetween the maximum SEM value and each of the at least two SEM valuesmeasured around the anatomical site; and flagging the relativemeasurement locations associated with a difference greater than apredetermined value as damaged tissue. In another aspect, a differenceis determined between the maximum SEM value and a minimum SEM valuemeasured around the anatomical site.

In another aspect, the non-transitory computer readable medium maycomprise instructions stored thereon that when executed on a processor,may perform the steps of receiving a SEM value at an anatomical site,and at least two SEM values measured around the anatomical site andtheir relative measurement locations; determining an average SEM valuefor each group of SEM values measured at approximately equidistance fromthe anatomical site; determining a maximum SEM value from the averageSEM values; determining a difference between the maximum average SEMvalue and each of the average SEM values measured around the anatomicalsite; and flagging the relative measurement locations associated with adifference greater than a predetermined value as damaged tissue.

In a further aspect, the present disclosure provides for, and includes,methods for identifying damaged tissue. A method according to thepresent disclosure may comprise measuring at least three sub-epidermalmoisture values at and around an anatomical site using an apparatus thatmay comprise one or more electrodes that may be capable of interrogatingtissue at and around an anatomical site, wherein each of the one or moreelectrodes may be configured to emit and receive a radiofrequency signalto generate a bioimpedance signal; a circuit that may be electronicallycoupled to the one or more electrodes and configured to convert thebioimpedance signal into a SEM value; a processor that may beelectronically coupled to the circuit and configured to receive the SEMvalue; and a non-transitory computer readable medium that may beelectronically coupled to the processor and may comprise instructionsstored thereon that when executed on the processor, may perform thesteps of receiving from the processor a SEM value measured at theanatomical site and at least two SEM values measured around theanatomical site and their relative measurement locations; determining amaximum SEM value from the measurements around the anatomical site;determining a difference between the maximum SEM value and each of theat least two SEM values measured around the anatomical site; andflagging the relative measurement locations associated with a differencegreater than a predetermined value as damaged tissue. In another aspect,a difference is determined between the maximum SEM value and a minimumSEM value measured around the anatomical site. The method may furthercomprise obtaining the relative measurement locations flagged as damagedtissue from the apparatus.

In another aspect, a method according to the present disclosure maycomprise measuring at least three sub-epidermal moisture values at andaround an anatomical site using an apparatus that may comprise one ormore electrodes that may be capable of interrogating tissue at andaround an anatomical site, wherein each of the one or more electrodesmay be configured to emit and receive a radiofrequency signal togenerate a bioimpedance signal; a circuit that may be electronicallycoupled to the one or more electrodes and configured to convert thebioimpedance signal into a SEM value; a processor that may beelectronically coupled to the circuit and configured to receive the SEMvalue; and a non-transitory computer readable medium that may beelectronically coupled to the processor and may comprise instructionsstored thereon that, when executed on the processor, may perform thesteps of receiving from the processor a SEM value measured at theanatomical site and at least two SEM values measured around theanatomical site and their relative measurement locations; determining anaverage SEM value for each group of SEM values measured at approximatelyequidistance from the anatomical site; determining a maximum SEM valuefrom the average SEM values; determining a difference between themaximum average SEM value and each of the average SEM values measuredaround the anatomical site; and flagging the relative measurementlocations associated with a difference greater than a predeterminedvalue as damaged tissue. The method may further comprise obtaining therelative measurement locations flagged as damaged tissue from theapparatus.

In a further aspect, the present disclosure provides for, and includes,methods for generating a SEM image indicating damaged tissue on ananatomical graphical representation. The SEM image may be generated byacquiring parameters of an anatomical site to be interrogated; measuringat least three sub-epidermal moisture values at and around an anatomicalsite using an apparatus that may comprise one or more electrodes thatmay be capable of interrogating tissue at and around an anatomical site,wherein each of the one or more electrodes may be configured to emit andreceive a radiofrequency signal to generate a bioimpedance signal; acircuit that may be electronically coupled to the one or more electrodesand configured to convert the bioimpedance signal into a SEM value; aprocessor that may be electronically coupled to the circuit andconfigured to receive the SEM value; and a non-transitory computerreadable medium that may be electronically coupled to the processor andmay comprise instructions stored thereon that when executed on theprocessor, may perform the steps of receiving from the processor a SEMvalue measured at the anatomical site, and at least two SEM valuesmeasured around anatomical site and their relative measurementlocations; determining a maximum SEM value from the measurements aroundthe anatomical site, determining a difference between the maximum SEMvalue and each of the at least two SEM values measured around theanatomical site; and flagging the relative measurement locationsassociated with a difference greater than a predetermined value asdamaged tissue. In another aspect, a difference is determined betweenthe maximum SEM value and a minimum SEM value measured around theanatomical site. The method may further comprise plotting the measuredSEM values in accordance with their relative measurement locations on agraphical representation of an area defined by the parameters of theanatomical site, and indicating the measurement locations that areflagged as damaged tissue.

In yet another aspect, the SEM image may be generated by acquiringparameters of an anatomical site to be interrogated; measuring at leastthree sub-epidermal moisture values at and around an anatomical siteusing an apparatus that may comprise one or more electrodes that may becapable of interrogating tissue at and around an anatomical site,wherein each of the one or more electrodes may be configured to emit andreceive a radiofrequency signal to generate a bioimpedance signal; acircuit that may be electronically coupled to the one or more electrodesand configured to convert the bioimpedance signal into a SEM value; aprocessor that may be electronically coupled to the circuit andconfigured to receive the SEM value; and a non-transitory computerreadable medium that may be electronically coupled to the processor andmay comprise instructions stored thereon that, when executed on theprocessor, may perform the steps of receiving from the processor a SEMvalue measured at the anatomical site, and at least two SEM valuesmeasured around anatomical site and their relative measurementlocations; determining an average SEM value for each group of SEM valuesmeasured at approximately equidistance from the anatomical site;determining a maximum SEM value from the average SEM values; determininga difference between the maximum average SEM value and each of theaverage SEM values measured around the anatomical site; and flagging therelative measurement locations associated with a difference greater thana predetermined value as damaged tissue. The method may further compriseplotting the measured SEM values in accordance with their relativemeasurement locations on a graphical representation of an area definedby the parameters of the anatomical site, and indicating the measurementlocations that is flagged as damaged tissue.

BRIEF DESCRIPTION OF THE FIGURES

Some aspects of the disclosure are herein described, by way of exampleonly, with reference to the accompanying drawings. With specificreference now to the drawings in detail, it is stressed that theparticulars shown are by way of example and are for purposes ofillustrative discussion of embodiments of the disclosure. In thisregard, the description, taken with the drawings, make apparent to thoseskilled in the art how aspects of the disclosure may be practiced.

FIG. 1—An exemplary apparatus according to the present disclosure,comprising one coaxial electrode.

FIG. 2—An exemplary sensing unit of the apparatus according to thepresent disclosure, comprising more than one coaxial electrode.

FIG. 3A—An exemplary coaxial electrode according to the presentdisclosure.

FIG. 3B—Exemplary coaxial electrodes constructed with a point sourceelectrode surrounded by six hexagon pad electrodes according to thepresent disclosure.

FIG. 3C—An exemplary array of hexagon pad electrodes where each of theelectrodes may be programmed to function as different parts of a coaxialelectrode in accordance with the present disclosure.

FIG. 3D—Sample electronic connection of an array of hexagonal padelectrodes allowing for coaxial electrode emulation in accordance withthe present disclosure.

FIG. 3E—An exemplary array of coaxial electrodes electronically coupledtogether.

FIG. 4—A sample measurement scheme according to the present disclosure.

FIG. 5A—Sample SEM measurement results obtained in accordance with themethods in the present disclosure, represented as a SEM map.

FIG. 5B—Sample SEM measurement results along the x-axis of FIG. 5Aplotted on a graph.

FIG. 5C—Sample SEM measurement results along the y-axis of FIG. 5Aplotted on a graph.

FIG. 6A—An exemplary method for taking SEM measurements starting at theposterior heel.

FIG. 6B—An exemplary method for taking SEM measurements starting at thelateral heel.

FIG. 6C—An exemplary method for taking SEM measurements starting at themedial heel.

FIG. 7A—Sample visual assessment of damaged tissue around a sacrum.

FIG. 7B—Sample SEM measurement results of damaged tissue obtained inaccordance with the methods in the present disclosure.

FIG. 8A—Sample visual assessment of healthy tissue around a sacrum.

FIG. 8B—Sample SEM measurement results of healthy tissue obtained inaccordance with the methods in the present disclosure.

FIG. 9A—A sample SEM map obtained in accordance with the methods in thepresent disclosure.

FIG. 9B—Corresponding visual assessment of damaged tissue of FIG. 9A.

FIG. 10—A sample SEM image obtained in accordance with the methods inthe present disclosure.

FIG. 11—Sample time-lapsed SEM images showing the sensitivity of thedetection apparatuses and methods in the present disclosure.

FIG. 12A—A sample graphical representation of a finite element modelshowing the depth of various SEM levels in accordance with the methodsin the present disclosure.

FIG. 12B—A sample plot of SEM measurements at various depth of askin-like material.

DETAILED DESCRIPTION

This description is not intended to be a detailed catalog of all thedifferent ways in which the disclosure may be implemented, or all thefeatures that may be added to the instant disclosure. For example,features illustrated with respect to one embodiment may be incorporatedinto other embodiments, and features illustrated with respect to aparticular embodiment may be deleted from that embodiment. Thus, thedisclosure contemplates that in some embodiments of the disclosure, anyfeature or combination of features set forth herein can be excluded oromitted. In addition, numerous variations and additions to the variousembodiments suggested herein will be apparent to those skilled in theart in light of the instant disclosure, which do not depart from theinstant disclosure. In other instances, well-known structures,interfaces, and processes have not been shown in detail in order not tounnecessarily obscure the invention. It is intended that no part of thisspecification be construed to effect a disavowal of any part of the fullscope of the invention. Hence, the following descriptions are intendedto illustrate some particular embodiments of the disclosure, and not toexhaustively specify all permutations, combinations and variationsthereof.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this disclosure belongs. The terminology used in thedescription of the disclosure herein is for the purpose of describingparticular embodiments only and is not intended to be limiting of thedisclosure.

All publications, patent applications, patents and other referencescited herein are incorporated by reference in their entireties for theteachings relevant to the sentence and/or paragraph in which thereference is presented. References to techniques employed herein areintended to refer to the techniques as commonly understood in the art,including variations on those techniques or substitutions of equivalenttechniques that would be apparent to one of skill in the art.

Unless the context indicates otherwise, it is specifically intended thatthe various features of the disclosure described herein can be used inany combination. Moreover, the present disclosure also contemplates thatin some embodiments of the disclosure, any feature or combination offeatures set forth herein can be excluded or omitted.

The methods disclosed herein comprise one or more steps or actions forachieving the described method. The method steps and/or actions may beinterchanged with one another without departing from the scope of thepresent invention. In other words, unless a specific order of steps oractions is required for proper operation of the embodiment, the orderand/or use of specific steps and/or actions may be modified withoutdeparting from the scope of the present invention.

As used in the description of the disclosure and the appended claims,the singular forms “a,” “an” and “the” are intended to include theplural forms as well, unless the context clearly indicates otherwise.

As used herein, “and/or” refers to and encompasses any and all possiblecombinations of one or more of the associated listed items, as well asthe lack of combinations when interpreted in the alternative (“or”).

The terms “about” and “approximately” as used herein when referring to ameasurable value such as a length, a frequency, or a SEM value and thelike, is meant to encompass variations of ±20%, ±10%, ±5%, ±1%, ±0.5%,or even ±0.1% of the specified amount.

As used herein, phrases such as “between X and Y” and “between about Xand Y” should be interpreted to include X and Y. As used herein, phrasessuch as “between about X and Y” mean “between about X and about Y” andphrases such as “from about X to Y” mean “from about X to about Y.”

The terms “comprise,” “comprises,” and “comprising” as used herein,specify the presence of the stated features, integers, steps,operations, elements, and/or components, but do not preclude thepresence or addition of one or more other features, integers, steps,operations, elements, components, and/or groups thereof.

As used herein, the transitional phrase “consisting essentially of”means that the scope of a claim is to be interpreted to encompass thespecified materials or steps recited in the claim and those that do notmaterially affect the basic and novel characteristic(s) of the claimeddisclosure. Thus, the term “consisting essentially of” when used in aclaim of this disclosure is not intended to be interpreted to beequivalent to “comprising.”

As used herein, the term “sub-epidermal moisture” refers to the increasein tissue fluid and local edema caused by vascular leakiness and otherchanges that modify the underlying structure of the damaged tissue inthe presence of continued pressure on tissue, apoptosis, necrosis, andthe inflammatory process.

As used herein, a “system” may be a collection of devices in wired orwireless communication with each other.

As used herein, “interrogate” refers to the use of radiofrequency energyto penetrate into a patient's skin.

As used herein a “patient” may be a human or animal subject.

An exemplary apparatus according to the present disclosure is shown inFIGS. 1 and 2. It will be understood that these are examples of anapparatus for measuring sub-epidermal moisture (“SEM”). In someembodiments, the apparatus according to the present disclosure may be ahandheld device, a portable device, a wired device, a wireless device,or a device that is fitted to measure a part of a human patient. U.S.Publication No. 2014/0288397 A1 to Sarrafzadeh et al. is directed to aSEM scanning apparatus, which is incorporated herein by reference in itsentirety.

In certain embodiments according to the present disclosure, theapparatus may comprise one or more electrodes. In one aspect accordingto the present disclosure, it may be preferable to use coaxialelectrodes over electrodes such as tetrapolar ECG electrodes becausecoaxial electrodes are generally isotropic, which may allow SEM valuesto be taken irrespective of the direction of electrode placement. TheSEM values measured by coaxial electrodes may also be representative ofthe moisture content of the tissue underneath the coaxial electrodes,rather than the moisture content of the tissue surface across twobi-polar electrodes spaced apart. In some embodiments, the apparatus maycomprise two or more coaxial electrodes, three or more coaxialelectrodes, four or more coaxial electrodes, five or more coaxialelectrodes, ten or more coaxial electrodes, fifteen or more coaxialelectrodes, twenty or more coaxial electrodes, twenty five or morecoaxial electrodes, or thirty or more coaxial electrodes. In someembodiments, the aforementioned coaxial electrodes may be configured toemit and receive an RF signal at a frequency of 32 kilohertz (kHz). Inother embodiments, the coaxial electrodes may be configured to emit andreceive an RF signal at a frequency of from about 5 kHz to about 100kHz, from about 10 kHz to about 100 kHz, from about 20 kHz to about 100kHz, from about 30 kHz to about 100 kHz, from about 40 kHz to about 100kHz, from about 50 kHz to about 100 kHz, from about 60 kHz to about 100kHz, from about 70 kHz to about 100 kHz, from about 80 kHz to about 100kHz, or from about 90 kHz to about 100 kHz. In yet another embodiment,the coaxial electrodes may be configured to emit and receive an RFsignal at a frequency of from about 5 kHz to about 10 kHz, from about 5kHz to about 20 kHz, from about 5 kHz to about 30 kHz, from about 5 kHzto about 40 kHz, from about 5 kHz to about 50 kHz, from about 5 kHz toabout 60 kHz, from about 5 kHz to about 70 kHz, from about 5 kHz toabout 80 kHz, or from about 5 kHz to about 90 kHz. In a furtherembodiment, the coaxial electrodes may be configured to emit and receivean RF signal at a frequency less than 100 kHz, less than 90 kHz, lessthan 80 kHz, less than 70 kHz, less than 60 kHz, less than 50 kHz, lessthan 40 kHz, less than 30 kHz, less than 20 kHz, less than 10 kHz, orless than 5 kHz. In certain embodiments, all of the coaxial electrodesof the apparatus may operate at the same frequency. In some embodiments,some of the coaxial electrodes of the apparatus may operate at differentfrequencies. In certain embodiments, the frequency of a coaxialelectrode may be changed through programming specific pins on anintegrated circuit in which they are connected.

In some embodiments according to the present disclosure, the coaxialelectrodes may comprise a bipolar configuration having a first electrodecomprising an outer annular ring disposed around a second inner circularelectrode. Referring to FIG. 3A, the outer ring electrode may have anouter diameter D_(o) and an inner diameter D_(I) that is larger than thediameter D_(c) of the circular inner electrode. Each inner circularelectrode and outer electrode may be coupled electrically to one or morecircuits that are capable of applying a voltage waveform to eachelectrode; generating a bioimpedance signal; and converting thecapacitance signal to a SEM value. In certain embodiments, thebioimpedance signal may be a capacitance signal generated by, e.g.,measuring the difference of the current waveform applied between thecentral electrode and the annular ring electrode. In some embodiments,the conversion may be performed by a 24 bit capacitance-to-digitalconverter. In another embodiment, the conversion may be a 16 bitcapacitance-to-digital converter, a charge-timing capacitance to digitalconverter, a sigma-delta capacitance to digital converter. The one ormore circuits may be electronically coupled to a processor. Theprocessor may be configured to receive the SEM value generated by thecircuit.

In certain embodiments, the one or more coaxial electrodes may have thesame size. In other embodiments, the one or more coaxial electrodes mayhave different sizes, which may be configured to interrogate thepatient's skin at different depths. The dimensions of the one or morecoaxial electrodes may correspond to the depth of interrogation into thederma of the patient. Accordingly, a larger diameter electrode maypenetrate deeper into the skin than a smaller pad. The desired depth mayvary depending on the region of the body being scanned, or the age, skinanatomy or other characteristic of the patient. In some embodiments, theone or more coaxial electrodes may be coupled to two or more separatecircuits to allow independent operation of each of the coaxialelectrodes. In another embodiment, all, or a subset, of the one or morecoaxial electrodes may be coupled to the same circuit.

In some embodiments, the one or more coaxial electrodes may be capableof emitting RF energy to a skin depth of 4 millimeters (mm), 3.5 mm, 3.0mm, 2.5 mm, 2.0 mm, 1.0 mm, or 0.5 mm. In a further embodiment, the oneor more coaxial electrodes may have an outer diameter D_(o) from about 5mm to about 55 mm, from about 10 mm to about 50 mm, from about 15 mm toabout 45 mm, or from about 20 mm to about 40 mm. In another embodiment,the outer ring of the one or more coaxial electrodes may have an innerdiameter D_(I) from about 4 mm to about 40 mm, from about 9 mm to about30 mm, or from about 14 mm to about 25 mm. In yet another embodiment,the inner electrode of the one or more coaxial electrodes may have adiameter D_(c) from about 2 mm to 7 mm, 3 mm to 6 mm, or 4 mm to 5 mm.

In a further embodiment, the one or more coaxial electrodes may bespaced apart at a distance to avoid interference between the electrodes.The distance may be a function of sensor size and frequency to beapplied. In some embodiments, each of the one or more coaxial electrodesmay be activated sequentially. In certain embodiments, multiple coaxialelectrodes may be activated at the same time.

In certain embodiments according to the present disclosure, a coaxialelectrode may comprise a point source surrounded by hexagon padelectrodes spaced at approximately equidistance, as illustrated in FIG.3B. The point source may comprise a hexagon pad electrode. In someembodiments, the point source may comprise two, three, four, five, orsix hexagon pad electrodes. In certain embodiments, a point source maybe surrounded by six hexagon pad electrodes. In some embodiments,multiple coaxial electrodes may be emulated from an array comprising aplurality of hexagon pad electrodes, where each hexagon pad electrodemay be programmed to be electronically coupled to a floating ground, acapacitance input, or a capacitance excitation signal, as illustrated inFIGS. 3C and 3D. In a further embodiment, each of the hexagon padelectrodes may be connected to a multiplexer that may have a select linethat controls whether the hexagon pad electrode is connected to acapacitance input or a capacitance excitation signal. The multiplexermay also have an enable line that controls whether to connect thehexagon pad electrode to a floating ground. In certain embodiments, themultiplexer may be a pass-gate multiplexer. In some embodiments, the oneor more coaxial electrodes may be arranged as illustrated in FIG. 3E toleverage multiplexer technology. Without being limited to theory, thearrangement illustrated in FIG. 3E may limit interference between theone or more coaxial electrodes.

In certain embodiments, one or more coaxial electrodes may be embeddedon a first side of a non-conductive substrate. In some embodiments, thesubstrate may be flexible or hard. In certain embodiments, the flexiblesubstrate may comprise kapton, polyimide, or a combination thereof. Infurther embodiments, an upper coverlay may be positioned directly abovethe one or more coaxial electrodes. In certain embodiments, the uppercoverlay may be a double-sided, copper-clad laminate and anall-polyimide composite of a polyimide film bonded to copper foil. Insome embodiments, the upper coverlay may comprise Pyralux 5 mil FR0150.Without being limited by theory, the use this upper coverlay may avoidparasitic charges naturally present on the skin surface from interferingwith the accuracy and precision of SEM measurements. In someembodiments, the one or more coaxial electrodes may be spring mounted toa substrate within an apparatus according to the present disclosure.

In some embodiments, the apparatus may comprise a non-transitorycomputer readable medium electronically coupled to the processor. Incertain embodiments, the non-transitory computer readable medium maycomprise instructions stored thereon that, when executed on a processor,may perform the steps of: (1) receiving at least one SEM value at ananatomical site; (2) receiving at least two SEM values measured aroundthe anatomical site and their relative measurement locations; (3)determining a maximum SEM value from the measurements around theanatomical site; (4) determining a difference between the maximum SEMvalue and each of the at least two SEM values measured around theanatomical site; and (5) flagging the relative measurement locationsassociated with a difference greater than a predetermined value asdamaged tissue. In another embodiment, the non-transitory computerreadable medium may comprise instructions stored thereon that may carryout the following steps when executed by the processor: (1) receiving atleast one SEM value measured at an anatomical site; (2) receiving atleast two SEM values measured around the anatomical site, and theirrelative measurement locations; (3) determining an average SEM value foreach group of SEM values measured at approximately equidistance from theanatomical site; (4) determining a maximum SEM value from the averageSEM values; (5) determining a difference between the maximum average SEMvalue and each of the average SEM values measured around the anatomicalsite; and (6) flagging the relative measurement locations associatedwith a difference greater than a predetermined value as damaged tissue.In yet another embodiment, the non-transitory computer readable mediummay comprise instructions stored thereon that, when executed on aprocessor, may perform the steps of: (1) receiving at least one SEMvalue at an anatomical site; (2) receiving at least two SEM valuesmeasured around the anatomical site and their relative measurementlocations; (3) determining a maximum SEM value from the measurementsaround the anatomical site; (4) determining a minimum SEM value from themeasurements around the anatomical site; (5) determining a differencebetween the maximum SEM value and the minimum SEM value; and (6)flagging the relative measurement locations associated with a differencegreater than a predetermined value as damaged tissue. In someembodiments, the predetermined value may be 0.3, 0.35, 0.4, 0.45, 0.5,0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0, 1.1, 1.2, 1.3,1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7,2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1,4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0, 5.1, 5.2, 5.3, 5.4, 5.5,5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9,7.0, 7.1, 7.2, 7.3, 7.4, or 7.5. It will be understood that thepredetermined value is not limited by design, but rather, one ofordinary skill in the art would be capable of choosing a predeterminedvalue based on a given unit of SEM.

In further embodiments, the leading edge of inflammation may beindicated by an SEM difference that is equal to or greater than thepredetermined value. In some embodiments, the leading edge ofinflammation may be identified by the maximum values out of a set of SEMmeasurements.

In certain embodiments, an anatomical site may be a bony prominence. Infurther embodiments, an anatomical site may be a sternum, sacrum, aheel, a scapula, an elbow, an ear, or other fleshy tissue. In someembodiments, one SEM value is measured at the anatomical site. Inanother embodiment, an average SEM value at the anatomical site isobtained from two, three, four, five, six, seven, eight, nine, ten, ormore than ten SEM values measured at the anatomical site.

The apparatuses of the present disclosure may allow the user to controlthe pressure applied onto a patient's skin to allow for optimizedmeasurement conditions. In certain embodiments, a first pressure sensormay be placed on a second side opposing the first side of the substratethat the coaxial electrodes are disposed on. In a further embodiment, asecond pressure sensor may be disposed on a second side opposing thefirst side of the substrate that the coaxial electrodes are disposed on.In certain embodiments, the first pressure sensor may be a low pressuresensor, and the second pressure sensor may be a high pressure sensor.Together, the first and second pressure sensors may allow measurementsto be taken at a predetermined range of target pressures. In someembodiments, a target pressure may be about 500 g. It will be understoodthat the high and low pressure sensors are not limited by design, butrather, one of ordinary skill in the art would be capable of choosingthese sensors based on a given range of target pressures. The first andsecond pressure sensors may be resistive pressure sensors. In someembodiments, the first and second pressure sensors may be sandwichedbetween the substrate and a conformal pressure pad. The conformalpressure pad may provide both support and conformity to enablemeasurements over body curvature and bony prominences.

In an embodiment, the apparatus may further comprise a plurality ofcontact sensors on the same planar surface as, and surrounding, each ofthe one or more coaxial electrodes to ensure complete contact of the oneor more coaxial electrodes to the skin surface. The plurality of contactsensors may be a plurality of pressure sensors, a plurality of lightsensors, a plurality of temperature sensors, a plurality of pH sensors,a plurality of perspiration sensors, a plurality of ultrasonic sensors,a plurality of bone growth stimulator sensors, or a plurality of acombination of these sensors. In some embodiments, the plurality ofcontact sensors may comprise four, five, six, seven, eight, nine, or tenor more contact sensors surrounding the one or more coaxial electrodes.

In certain embodiments, the apparatus may comprise a temperature probe.In some embodiments, the temperature probe may be a thermocouple or aninfrared thermometer.

In some embodiments, the apparatus may further comprise a display havinga user interface. The user interface may allow the user to inputmeasurement location data. The user interface may further allow the userto view measured SEM values and/or damaged tissue locations. In certainembodiments, the apparatus may further comprise a transceiver circuitconfigured to receive data from and transmit data to a remote device,such as a computer, tablet or other mobile or wearable device. Thetransceiver circuit may allow for any suitable form of wired or wirelessdata transmission such as, for example, USB, Bluetooth, or Wifi.

Methods according to the present disclosure provide for identifyingdamaged tissue. In some embodiments, the method may comprise measuringat least three SEM values at and around an anatomical site using anapparatus of the present invention, and obtaining from the apparatusmeasurement locations that are flagged as damaged tissue. In certainembodiments, measurements may be taken at positions that are located onone or more concentric circles about an anatomic site. FIG. 4 provides asample measurement strategy, with the center being defined by ananatomic site. In another embodiments, the measurements may be takenspatially apart from an anatomic site. In yet another embodiment, themeasurements may be taken on a straight line across an anatomic site. Ina further embodiment, the measurements may be taken on a curve around ananatomic site. In certain embodiment, surface moisture and matter abovea patient's skin surface may be removed prior to the measuring step. Insome embodiments, the measuring step may take less than one second, lessthan two seconds, less than three seconds, less than four seconds, orless than five seconds.

Having now generally described the invention, the same will be morereadily understood through reference to the following examples that areprovided by way of illustration, and are not intended to be limiting ofthe present disclosure, unless specified.

EXAMPLES Example 1 Measuring Sub-Epidermal Moisture (SEM) Values at theBony Prominence of the Sacrum

Subjects with visually-confirmed Stage I or II pressure ulcers withunbroken skin were subjected to multiple SEM measurements at and aroundthe boney prominence of the sacrum using an apparatus of thisdisclosure. Prior to performing the measurements, surface moisture andmatter above the subjects' skin surface were removed. An electrode ofthe apparatus was applied to the desired anatomical site with sufficientpressure to ensure complete contact for approximately one second.Additional measurements were taken at the mapped location as laid out inFIG. 4.

FIG. 5A shows a sample SEM map centered on an anatomical site. FIG. 5Bis a plot of the individual SEM values across the x-axis of the SEM map.FIG. 5C is a plot of the individual SEM values across the y-axis of theSEM map. Damaged tissue radiated from the center anatomical site to anedge of erythema defined by a difference in SEM values of greater than0.5.

Example 2 Taking SEM Measurements at the Bony Prominence of the Heel

SEM measurements were taken at the heel using one of three methods belowto ensure complete contact of an electrode with the skin of a humanpatient.

FIG. 6A illustrates a method used to take SEM measurements starting atthe posterior heel using an apparatus according to the presentdisclosure. First, the forefoot was dorsiflexed such that the toes werepointing towards the shin. Second, an electrode was positioned at thebase of the heel. The electrode was adjusted for full contact with theheel, and multiple SEM measurements were then taken in a straight linetowards the toes.

FIG. 6B illustrates a method used to take SEM measurements starting atthe lateral heel using an apparatus according to the present disclosure.First, the toes were pointed away from the body and rotated inwardtowards the medial side of the body. Second, an electrode was placed onthe lateral side of the heel. The electrode was adjusted for fullcontact with the heel, and multiple SEM measurements were taken in astraight line towards the bottom of the foot.

FIG. 6C illustrates a method used to take SEM measurements starting atthe medial heel using an apparatus according to the present disclosure.First, the toes were pointed away from the body and rotated outwardstoward the lateral side of the body. Second, the electrode was placed onthe medial side of the heel. The electrode was adjusted for full contactwith the heel, and multiple measurements were taken around the back ofthe heel in a curve.

Example 3 Identifying a Region of Damaged Tissue

SEM measurements were taken on a straight line, each spaced apart by 2cm, across the sacrum of a patient. Multiple measurements were taken ata given measurement location. FIG. 7A is a sample visual assessment ofdamaged tissue. FIG. 7B is a corresponding plot of the averages of SEMmeasurements taken at each location. The edges of erythema are definedby differences in SEM values of greater than 0.5.

Example 4 SEM Measurements of Healthy Tissue

SEM measurements were taken on a straight line across the sacrum of apatient. Multiple measurements were taken at a given measurementlocation. FIG. 8A is a sample visual assessment of healthy tissue. FIG.8B is a corresponding plot of the averages of SEM measurements taken ateach location. The tissue is defined as healthy as the differences inSEM values are all less than 0.5.

Example 5 SEM Measurement Map of Damaged Tissue

SEM measurements were taken in accordance with Example 1. FIG. 9A is asample map of averaged SEM values taken on concentric rings around ananatomical site. FIG. 9B is the corresponding visual assessment of thepatient's skin. Compromised tissue is identified by the solid circle,where the difference in SEM values compared to the maximum SEM value isgreater than 0.5. The leading edge of inflammation is identified by thedotted circle, where the difference in SEM values compared to themaximum SEM value is equal to or greater than 0.5. The leading edge ofinflammation is identified by a dotted line, indicating the largestvalues in the SEM map.

Example 6 Sample SEM Measurement Image Representations

SEM measurements were taken with an array of coaxial electrodes. FIG. 10is a sample output of a SEM measurement image showing the moisturecontent of the skin over a defined area. Different SEM values areindicated by different colors.

Example 7 SEM Measurements of Skin Moisture Content Over Time

Moisturizer was used to simulate the onset of a pressure ulcer. 0.2 mLmoisturizer was applied to the inner forearm of a subject for 60seconds. The moisturizer was then wiped from the skin. SEM measurementswere taken with an array of coaxial electrodes every 10 minutes for 2hours. FIG. 11 shows a sample time lapse of an SEM measurement image tomonitor moisture content of a test subject.

Example 8 Selecting an Optimal Electrode for Interrogating Patient Skin

FIG. 12A is a sample graphical representation of a finite element modelshowing the depth of various SEM levels in accordance with the methodsin the present disclosure. Each line indicates a SEM value and the depthof the moisture content.

Actual SEM levels in various depths of a skin-like material weremeasured using an apparatus according to the present disclosure.Specifically, the apparatus comprises one coaxial electrode. First, thethickness of a blister bandage, which simulates a skin-like material,was measured and placed on the coaxial electrode. A downward force wasthen applied via a metal onto the coaxial electrode, in an acceptablerange according to the present disclosure. The metal is fitted to asecond metal in tubular form. The second metal was selected from brass,aluminum, and stainless steel. The SEM measurement was recorded.Additional blister bandages were placed atop the coaxial electrodes forfurther SEM measurement recordings. FIG. 12B is a sample plot of SEMmeasurements at various thicknesses of the blister bandages. Withoutbeing limited by theory, the variations in the SEM values in thepresence of different tubular metal may be due to potential magneticfield interference. The maximum depth of a magnetic field generated bythe coaxial sensor was determined by the distance from the coaxialsensor when the metal tube no longer interfered with the magnetic field.In this example, the maximum depth ranged from 0.135 inches to 0.145inches. Accordingly, electrodes having an optimal penetration depthcould be selected to interrogate specific depths of patient skin.

While the invention has been described with reference to particularembodiments, it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted forelements thereof without departing from the scope of the invention. Inaddition, many modifications may be made to a particular situation ormaterial to the teachings of the invention without departing from thescope of the invention.

Therefore, it is intended that the invention not be limited to theparticular embodiments disclosed as the best mode contemplated forcarrying out this invention, but that the invention will include allembodiments falling within the scope and spirit of the appended claims.

1.-22. (canceled)
 23. An apparatus for assessing tissue health, saidapparatus comprising: a plurality of coaxial electrodes embedded on afirst side of a substrate; a circuit electronically coupled to saidplurality of coaxial electrodes and configured to generate a pluralityof capacitance signals respectively associated with the plurality ofcoaxial electrodes; a processor electronically coupled to said circuitand configured to receive said plurality of capacitance signals andconvert said plurality of capacitance signal into a plurality ofSub-Epidermal Moisture (SEM) values respectively associated with theplurality of coaxial electrodes; and a non-transitory computer-readablemedium electronically coupled to said processor and comprisinginstructions stored thereon that, when executed on said processor,perform the steps of: receiving said plurality of SEM values associatedwith the plurality of coaxial electrodes; determining a maximum SEMvalue and a minimum SEM value from said received plurality of SEMvalues; determining a difference between said maximum SEM value and saidminimum SEM value, wherein said difference is an indicator related totissue health.
 24. The apparatus of claim 23, further comprising avisual display coupled to said processor, wherein said instructionsfurther comprise a step to provide said difference on said display. 25.The apparatus of claim 23, wherein said substrate is flexible.
 26. Theapparatus of claim 23, wherein said substrate is rigid.
 27. Theapparatus of claim 23, wherein: said plurality of coaxial electrodes areconfigured to interrogate tissue at a respective plurality ofmeasurement locations, and said non-transitory computer-readable mediumfurther comprises instructions stored thereon that, when executed onsaid processor, perform the step of flagging a measurement location of acoaxial electrode that is associated with one of said maximum and saidminimum SEM values.
 28. The apparatus of claim 23, further comprising asecond circuit configured to receive and transmit data to a remotedevice.
 29. The apparatus of claim 28, wherein the remote device is atablet or a mobile device.
 30. The apparatus of claim 23, furthercomprising a temperature probe.
 31. The apparatus of claim 23, furthercomprising a conformal pressure pad configured to provide both supportand conformity to a non-planar sensing surface.
 32. The apparatus ofclaim 31, further comprising a pressure sensor sandwiched between saidsubstrate and said conformal pressure pad.
 33. The apparatus of claim36, wherein said non-transitory computer-readable medium is configuredto perform the step of receiving when a pressure measured by thepressure sensor is within a defined pressure range.
 34. The apparatus ofclaim 23, further comprising an insulating cover layer coupled to theflexible substrate and configured to act as a barrier between the tissuebeing measured and the first and second electrodes.
 35. The apparatus ofclaim 23, wherein the one or more electrodes comprises a first electrodeand a second electrode, and wherein the second electrode is an annularelectrode that is disposed around the first electrode.
 36. The apparatusof claim 35, wherein the first electrode and the second electrode areconfigured such that there is an annular gap between the first andsecond electrodes.
 37. The apparatus of claim 36, wherein the annulargap is uniform.
 38. The apparatus of claim 35, wherein the first andsecond electrodes are electrically insulated from each other.
 39. Theapparatus of claim 23, wherein the instructions stored on said processorrequire receipt of at least three SEM values from different locationsprior to determining said maximum and minimum SEM values from saidreceived SEM values.
 40. An apparatus for assessing tissue health, saidapparatus comprising: a plurality of coaxial electrodes embedded on afirst side of a substrate; a circuit electronically coupled to said oneor more coaxial electrodes and configured to generate a plurality ofcapacitance signals respectively associated with the plurality ofcoaxial electrodes; a processor electronically coupled to said circuitand configured to receive said plurality of capacitance signals andconvert said plurality of capacitance signal into a plurality ofsub-epidermal moisture (SEM) values respectively associated with theplurality of coaxial electrodes; and a non-transitory computer-readablemedium electronically coupled to said processor and comprisinginstructions stored thereon that, when executed on said processor,perform the steps of: receiving at least two of said SEM valuesassociated with the plurality of coaxial electrodes; determining anaverage of said received SEM values; and determining a differencebetween one of said received SEM values and said average SEM value,wherein said difference is an indicator related to tissue health. 41.The apparatus of claim 40, wherein said instructions further comprise:determining a maximum SEM value from said received SEM values; anddetermining said difference between said maximum SEM value and saidaverage SEM value.
 42. The apparatus of claim 40, wherein saidinstructions further comprise: determining differences between each ofsaid received SEM values and said average SEM value.
 43. The apparatusof claim 40, wherein said substrate is flexible.
 44. The apparatus ofclaim 40, wherein said substrate is rigid.
 45. The apparatus of claim40, wherein: said plurality of coaxial electrodes are configured tointerrogate tissue at a respective plurality of measurement locations,and said non-transitory computer-readable medium further comprisesinstructions stored thereon that, when executed on said processor,perform the step of flagging a measurement location of a coaxialelectrode that is associated with one of said maximum and said minimumSEM values.
 46. The apparatus of claim 40, further comprising a secondcircuit configured to receive and transmit data to a remote device. 47.The apparatus of claim 46, wherein the remote device is a tablet or amobile device.
 48. The apparatus of claim 40, further comprising atemperature probe.
 49. The apparatus of claim 40, further comprising aconformal pressure pad configured to provide both support and conformityto a non-planar sensing surface.
 50. The apparatus of claim 49, furthercomprising a pressure sensor sandwiched between said substrate and saidconformal pressure pad.
 51. The apparatus of claim 50, wherein saidnon-transitory computer-readable medium is configured to perform thestep of receiving when a pressure measured by the pressure sensor iswithin a defined pressure range.
 52. The apparatus of claim 40, furthercomprising an insulating cover layer coupled to the flexible substrateand configured to act as a barrier between the tissue being measured andthe first and second electrodes.
 53. The apparatus of claim 40, whereinthe one or more electrodes comprises a first electrode and a secondelectrode, and wherein the second electrode is an annular electrode thatis disposed around the first electrode.
 54. The apparatus of claim 52,wherein the first electrode and the second electrode are configured suchthat there is an annular gap between the first and second electrodes.55. The apparatus of claim 53, wherein the annular gap is uniform. 56.The apparatus of claim 52, wherein the first and second electrodes areelectrically insulated from each other.